Use of nalbuphine as a substitute for butorphanol in combination with dexmedetomidine and tiletamine/zolazepam: a randomized non-inferiority trial

Abstract

Objectives The goal of this study was to determine whether a drug combination using nalbuphine with dexmedetomidine and tiletamine/zolazepam is non-inferior to one that uses butorphanol. Methods All healthy cats presenting solely for gonadectomy to two trap–neuter–return mobile clinic days were randomly assigned to induction with a combination of tiletamine/zolazepam 3 mg/kg, dexmedetomidine 7.5 µg/kg and either butorphanol or nalbuphine at 0.15 mg/kg. All participants were blinded to the identity of the combinations. The primary endpoint was clinician satisfaction, comprised of the mean of four satisfaction ratings on a 7-point Likert scale (highly dissatisfied through to highly satisfied) recorded for induction, maintenance of anesthesia, surgery and recovery. Exploratory endpoints included each individual score, number of injections, duration of induction, duration of recovery and need for reversal agent. To assess non-inferiority for the primary endpoint and individual scores, the difference and 95% confidence intervals (CIs) of the difference between the mean clinical scores for the nalbuphine and butorphanol-based combinations were calculated and compared with a prespecified non-inferiority margin of 20% (1.4 points). Results Seventy-two cats were enrolled, 36 in each group. The mean ± SD composite score for the combination with nalbuphine was 6.06 ± 0.59 (95% CI 5.86–6.25) points, while the combination with butorphanol was 6.22 ± 0.62 (95% CI 6.01–6.43). The difference between mean scores was 0.17 (–0.12 to 0.45), which did not exceed the prespecified boundary of 1.4, establishing the non-inferiority of nalbuphine. No individual clinical score for nalbuphine was inferior to butorphanol, and there were no significant differences for any secondary endpoints. Conclusions and relevance The clinical experience of the nalbuphine-based combination was non-inferior to the butorphanol-based combination. Nalbuphine is an effective substitute for butorphanol, providing another option if butorphanol is unavailable due to shortage, controlled status or cost, without requiring a change in anesthetic workflow.

Immediate Postoperative Analgesia of Nalbuphine-Ketamine Combination Compared with Ketamine Alone in Xylazine-Sedated Goats Undergoing Left Flank Laparotomy

“…The calm recovery without agitation associated with nalbuphine administration could be attributed to the fact that nalbuphine primarily acts on c-fiber nociceptors, not motor or sympathetic receptors [ 25 ]. In cats, nalbuphine-based anesthetic combination has also been shown to provide superior clinician satisfaction during gonadectomy [ 7 ].…”

“…Compared to the XK group, the XNK group showed a lower level of cortisol at TInd, TE (0), and ½, 1, 2, 4, 6, 12, and 24 h postoperatively, with a statistically significant decrease detected at ½ and 1 h timepoints. In prior studies, nalbuphine has been reported to enhance postoperative analgesia and decrease surgical stress and pain [ 7 , 31 , 42 ], which could be pivotal for reducing cortisol release. In this current study, the subjective immediate postoperative pain score almost correlated with the dynamic alteration which occurred in the serum cortisol concentration in both inductions.…”

“…In humans, nalbuphine is regarded as an important element of multimodal anesthesia and used as a pain-relieving medication for moderate and severe conditions, preoperative and postoperative analgesia, and gynecological interferences [ 6 ]. Nalbuphine has not been extensively used in veterinary practice, however, some studies of the use of nalbuphine have been reported in cats [ 7 ], dogs [ 8 , 9 ], horses [ 10 ], and camels [ 11 ], disclosing that nalbuphine could produce a superior analgesia without affecting cardiopulmonary variables.…”

River otter chemical immobilization and field surgery using nonscheduled drugs

“…Nalbuphine counteracts the respiratory depression of α 2 ‐agonists and provides additional analgesic effect (Schmidt et al 1985, Mills et al 1990, Kamal et al 2019). Although dexmedetomidine and nalbuphine have not been used together on river otters, they have been on dogs, cats, and humans (Nallam et al 2017, Nishimura et al 2018, Kreisler et al 2020) and in combination with other drugs for other otter species (Joseph et al 1987, Fiorello et al 2014). Medetomidine (Domitor® [medetomidine hydrochloride, Pfizer Animal Health, New York, NY, USA) is a drug closely related to dexmedetomidine (Ko et al 2009, Hoy and Keating 2011) and has been used to sedate otters in several studies (Spelman et al 1994, Fernandez‐Moran et al 2001, Soto‐Azat et al 2004, Soto‐Azat et al 2006).…”